Design and synthesis of α-naphthoflavone chimera derivatives able to eliminate cytochrome P450 (CYP)1B1-mediated drug resistance via targeted CYP1B1 degradation was written by Zhou, Li;Chen, Wenming;Cao, Chenyang;Shi, Yonghui;Ye, Wenchong;Hu, Jiliang;Wang, Ling Li;Zhou, Wen. And the article was included in European Journal of Medicinal Chemistry in 2020.Recommanded Product: 6294-17-3 The following contents are mentioned in the article:
Extrahepatic cytochrome P 450 1B1 (CYP1B1), which is highly expressed in various tumors, is an attractive and potential target for cancer prevention, therapy, and reversal of drug resistance. CYP1B1 inhibition is the current predominant therapeutic paradigm to treating CYP1B1-mediated malignancy, but therapeutic effect has little success. Herein, we reported CYP1B1 degradation in place of CYP1B1 inhibition for reversing drug resistance toward docetaxel in CYP1B1-overexpressing prostate cancer cell line DU145 using a PROTAC strategy. Replacing chlorine atom of a CYP1B1 selective inhibitor we found previously with ethynyl, we got the resulting α-naphthoflavone derivative 5 which kept strong inhibition against CYP1B1 (IC50 = 0.4±0.2 nM) and high selectivity. Coupling of 5 with thalidomide derivatives of varying chain lengths afforded conjugates 6A-6D via click reaction. In vitro cell-based assay indicated that 6C was more effective in eliminating drug resistance of CYP1B1-overexpressed DU145 cells compared with other analogs. Western blotting anal. showed CYP1B1 degradation was one main reason for the reversal of drug resistance to docetaxel and the effect was obtained in a concentration-dependent manner. This work is the first attempt to overcome CYP1B1-mediated drug resistance via CYP1B1 degradation instead of CYP1B1 inhibition, which could provide a new direction toward eliminating drug resistance. This study involved multiple reactions and reactants, such as 1-Bromo-6-chlorohexane (cas: 6294-17-3Recommanded Product: 6294-17-3).
1-Bromo-6-chlorohexane (cas: 6294-17-3) belongs to organic chlorides. Chlorination modifies the physical properties of hydrocarbons in several ways. These compounds are typically denser than water due to the higher atomic weight of chlorine versus hydrogen. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Recommanded Product: 6294-17-3
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics